Abnormal Nails and Hypohidrosis in a 22-Month-Old Boy

Abha Khandelwal, MS, MD, Rush University Medical Center, Chicago; Teri A. Kahn, MD, The Cleveland Clinic Foundation, Cleveland; and Anjeli G. Laungani, MD, Henry Ford Hospital, Detroit

Published Online: March 2, 2008 - 6:14:52 PM (CST)

Case Presentation

Figure 1 Thinning hair in a 22-month-old boy. Hypotrichosis or alopecia is a common manifestation of HED.

A 22-month-old boy presented to the clinic for an evaluation because of repeated otitis media and upper respiratory tract infections. He was born prematurely at 32 weeks, by a cesarean section, but had an otherwise uncomplicated gestation. Physical examination showed he had short coarse hair (Figure 1), frontal bossing and thinning of the lateral eyebrows (Figure 2), peg-shaped teeth (Figure 3), and thick, yellow dystrophic nails (Figure 4). His history included recurrent fevers and several episodes of pneumonia, suspected of immunodeficiency. Upon further questioning, the boy's mother reported that she had noted he had not been sweating as much as his siblings, and that his nails were dystrophic from birth. Of note, the patient's family history revealed that his father had Charcot-Marie-Tooth disease.

Figure 2 Frontal bossing, flattened nasal bridge, and thinning of lateral eyebrows are all characteristic of HED.

Histopathology of a palmar biopsy demonstrated a reduced number of eccrine glands and ducts, consistent with hypohidrotic ectodermal dysplasia (HED). Further immunoglobulin (Ig) testing revealed normal IgG, IgA, and IgM levels, indicating a good prognosis for this patient.

Treatment recommendations included the avoidance of vigorous physical activity to prevent hyperpyrexia, closely monitoring the patient for infection, a low threshold for starting antibiotics, and cosmetic surgery for physical features such as his teeth.

Discussion

Also known as Christ-Siemens-Touraine syndrome, HED can range from mild ectodermal dysplasia with limited involvement to severe disease associated with immunodeficiency, severe infections, hyperthermia, and even death.

Etiology and pathophysiology

Figure 3 Peg-shaped teeth is another typical sign of HED.

HED belongs to a large group of inherited disorders that impair the normal development of ectodermal structures. HED can be identified as early as birth from physical manifestations; in infants aged 6 to 9 months, when teeth fail to erupt or are conical in shape; but diagnosis can also be delayed till early childhood, when patients present with recurrent infections. Some milder forms may even go undiagnosed. Although no studies report exact age ranges, most reported cases indicate that the diagnosis is established between infancy and early childhood. In some cases, this aberration in development may also involve the mesodermal structures.¹

HED is the most common form of ectodermal dysplasias, which usually cause anomalies of hair, teeth, nails, and sweat glands, as seen in this boy, and can be associated with other entities, such as mental retardation. Although the genetic pattern in HED is most often expressed as X-linked recessive, autosomal dominant and autosomal recessive cases have also been reported.² The X-linked recessive form exhibits a 5:1 male to female predominance.³

Figure 4 Thick, yellow dystrophic nails of the boy?s fingers (A) and toes (B). Nail onychodystrophy and hyperkeratosis are common manifestations of HED.

Clinical manifestations
HED often manifests as a triad of defects involving hypodontia, hypotrichosis, and a partial or complete absence of eccrine or sebaceous glands. Facial features can demonstrate periorbital hyperpigmentation, a pointed chin, frontal bossing, flattened nasal bridge, and hypo/anodontia, as seen in this boy. The scalp hair is sparse and hypopigmented and generalized hypotrichosis or alopecia may occur, as also seen in this patient. Another common feature shown in our patient involves the nails, which may demonstrate onychodystrophy and hyperkeratosis.⁴ Studies have pointed out that the external auditory meatus may be abnormally narrow, leading to cerumen impaction and hearing impairment.¹

Patients diagnosed with HED have an increased susceptibility to otitis media, chronic pharyngitis, bronchitis, and rhinitis secondary to a lack of development of mucous glands and their protective secretions.^3,5 In addition, variants of HED can be associated with primary immunodeficiencies of IgG and poor antibody response to polysaccharide antigens. Such patients are susceptible to several organisms, including Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas, Haemophilus influenzae, herpes simplex virus, and mycobacteria. As demonstrated by several fatal case reports, these organisms can cause life-threatening infections in children that are mostly seen with disseminated Mycobacterium, Streptococcus, and herpes.⁶

Patients with HED often present with signs and symptoms such as fever of unknown origin or recurrent high fevers.³ Febrile episodes are often secondary to hypohidrosis.

Diagnosis
Lack of familiarity with HED can often lead to unnecessary testing. The diagnosis is based on the clinical manifestations, as outlined in the Table. A palmar skin biopsy confirms the diagnosis, showing decrease or absence of eccrine glands. Electron microscopy will often demonstrate pili torti or twisting of the hair fiber. Patients have a predilection to overheating, manifesting symptoms ranging from minor dehydration to severe febrile seizures and even death, secondary to hyperthermia and its associated electrolyte abnormalities.

Treatment
Management involves avoiding overheating and limiting exercise. In addition, physicians should monitor the patient for early signs of infection and have a low threshold for starting antipyretic and antibiotic therapy. Other interventions include methylcellulose for dry eyes and/or mucosa, or corrective dental measures.³

Management considerations for the immunodeficient type of HED may include antibiotic prophylaxis that targets the offending organism. Before surgical procedures, endocarditis prophylaxis may be initiated with amoxicillin; however, prophylaxis is variable and no definitive guidelines are available. For example, if the patient were to develop pneumonia, ceftriaxone may be used to cover Streptococcus and azithromycin to cover Haemophilus. Antibiotic use should be individualized, depending on the presence of occasional immunodeficiencies and what types of infections the patient has had in the past. If, for example, the patient has cellulitis, the physician may want to be sure they have covered staphylococcus. If the patient has had methicillin-resistant S aureus, vancomycin would be appropriate; if not, clindamycin may be sufficient along with replacement intravenous immunoglobulin. Avoidance of live vaccines is imperative for such variants.⁶

Prognosis for patients with HED varies and depends on the severity of the clinical manifestations. Patients may have stunted development, mental retardation, and maxillofacial, renal, or ocular abnormalities.

Early recognition of HED is critical for the initiation of a multidisciplinary therapeutic approach, with collaboration between the primary care physician/pediatrician, geneticist, dermatologist, ophthalmologist, otolaryngologist, oral and maxillofacial surgeon, and orthopedic surgeon.¹

Conclusion

Although a rare entity, all physicians should be aware of this syndrome to facilitate a prompt diagnosis. Initiating antibiotics earlier will prevent infection dissemination and minimize heat exposure. Genetic counseling for future pregnancies is also recommended. Appropriate lifestyle changes can prevent early death. Combined efforts of physicians from various specialties will reduce morbidity and mortality.

References

1. Mills R, Montague ML, Naysmith L. Ear, nose and throat manifestations of ectodermal dysplasia. J Laryngol Otol. 2004;118:406-408.
2. Shimomura Y, Sato N, Miyashita A, et al. A rare case of hypohidrotic ectodermal dysplasia caused by compound heterozygous mutations in the EDAR gene. J Invest Dermatol. 2004;123:649-655.
3. Hizli S, Ozdemir S, Bakkaloğlu A. Anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome) presenting as a fever of unknown origin in an infant. Int J Dermatol. 1998;37:132-134.
4. K?se O, Tastan H, Deveci S, et al. Anhidrotic ectodermal dysplasia with eruptive vellus hair cysts. Int J Dermatol. 2001;40:401-402.
5. Ghosh S, Das M. Hypohidrotic ectodermal dysplasia of sisters in a family. Indian Pediatr. 2004;41:1176-1177.
6. Carrol ED, Gennery AR, Flood TJ, et al. Anhidrotic ectodermal dysplasia and immunodeficiency: the role of NEMO. Arch Dis Child. 2003;88:340-341.